{
  "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a highly transmissible acute respiratory infection that can result in severe pneumonia and death. Many details of SARS-CoV-2 infection are not fully understood, including the cell biology and host-virus interactions involved in coronavirus assembly and release, in which the Envelope (E) structural protein is instrumental. Deletion of E in other coronaviruses has been shown previously to either attenuate or abrogate infection. To determine the role of E in SARS-CoV-2 virus production and infectivity, we produced a reporter SARS-CoV-2 with or without the E gene deleted using a bacterial artificial chromosome. Replication of ΔE SARS-CoV-2 was attenuated in Vero E6 cells expressing human ACE2 and TMPRSS2 and in human epithelial cell lines. Electron and immunofluorescence microscopy and virology assays showed that ΔE SARS-CoV-2 increased cell surface expression of Spike (S) glycoprotein, leading to reduced S incorporation into ΔE SARS-CoV-2 particles and promotion of increased cell-to-cell transmission that evades neutralizing antibody inhibition. Trans-complementation of E partially rescued ΔE SARS-CoV-2 S incorporation and restored cell-free transmission. In addition to validating the role of E in retention of S in the ER-Golgi intermediate complex (ERGIC), our results showed that a lack of E led to reorganization of the ERGIC and Golgi during SARS-CoV-2 infection. Improved understanding of E in SARS-CoV-2 replication and host pathogenesis may help the development of novel therapeutics.\n\nIMPORTANCE: Non-Spike coronavirus structural proteins, including Envelope, are conserved, making them potential pan-coronavirus therapeutic targets. Many details about these proteins and their roles in viral replication and host pathogenesis are unknown. In this study, we showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates without Envelope but is attenuated and impaired in virus particle formation, with less Spike incorporated into virions and more Spike expressed on the cell surface compared to wild-type virus. SARS-CoV-2 lacking Envelope transmitted primarily via cell fusion and evaded neutralizing antibodies. In addition, the absence of Envelope resulted in the reorganization of the cell secretory compartment during SARS-CoV-2 infection. A better understanding of how Envelope influences SARS-CoV-2 replication could guide directed design of novel therapeutics for treatment of COVID-19 patients, as well as the potential for pan-coronavirus protection against future coronavirus outbreaks.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine",
    "Center for Vaccine Research, University of Pittsburgh",
    "Department of Cell Biology, University of Pittsburgh School of Medicine",
    "Department of Structural Biology, University of Pittsburgh School of Medicine"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Hannah L. Fischer",
      "orcid": "0000-0002-8267-6308"
    },
    {
      "affs": [
        0
      ],
      "name": "Shanmugapriya Shanmugapriya"
    },
    {
      "affs": [
        0
      ],
      "name": "Christopher Kline"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "W. Paul Duprex",
      "orcid": "0000-0003-1716-6376"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kevin R. McCarthy",
      "orcid": "0000-0003-1016-6015"
    },
    {
      "affs": [
        2
      ],
      "name": "Simon C. Watkins"
    },
    {
      "affs": [
        3
      ],
      "name": "James F. Conway"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zandrea Ambrose",
      "orcid": "0000-0002-8610-2766"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ez2yqrhmqgmd0.bib",
  "cited_by": 0,
  "doi": "10.1128/mbio.01574-26",
  "fulltext_url": null,
  "id": "ez2yqrhmqgmd0",
  "issns": [
    "2150-7511"
  ],
  "landing_url": "https://journals.asm.org/doi/10.1128/mbio.01574-26",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": "https://journals.asm.org/doi/pdf/10.1128/mbio.01574-26",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": "American Society for Microbiology",
  "ris": "https://research.draconitic.com/paper/ez2yqrhmqgmd0.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T00:25:43Z",
      "native_id": "10.1128/mbio.01574-26",
      "source": "crossref",
      "url": "https://journals.asm.org/doi/10.1128/mbio.01574-26"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:2150-7511",
      "subfield": "microbiology"
    }
  ],
  "title": "Deletion of the Envelope gene attenuates SARS-CoV-2 infection by altered spike localization and increased cell-to-cell transmission",
  "title_text": "Deletion of the Envelope gene attenuates SARS-CoV-2 infection by altered spike localization and increased cell-to-cell transmission",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T00:21:03Z",
  "url": "https://research.draconitic.com/paper/ez2yqrhmqgmd0",
  "venue": "mBio",
  "versions": []
}